MXPA06005538A

MXPA06005538A - Device and method for analysing a liquid sample.

Info

Publication number: MXPA06005538A
Application number: MXPA06005538A
Authority: MX
Inventors: Heinz Werner Busch; Udo Heinrich Grabowy
Original assignee: Raumedic Ag
Priority date: 2003-11-19
Filing date: 2004-11-18
Publication date: 2006-12-14
Also published as: RU2006116548A; MY135482A; DE502004004832D1; EP1685388B9; EP1685388A2; CA2545643A1; ATE371859T1; EP1685388B1; WO2005050183A3; ES2293367T3; WO2005050183A2

Abstract

The inventive device for analysing a liquid sample by titration comprises a light source (2), a light sensor (3), a measuring head (1) which is immersible in the examined liquid sample and provided with a waveguide for absorbing the light from the light source (2) and guiding said light to the light sensor (3), wherein said measuring head (1) is provided with a cavity (5) which comprises a light guide interruption and in which the studied liquid penetrates when the measuring head (1) is immersed and wherein the light guide can be separated from the light source (2) and the light sensor (3).

Description

appropriate for the determination of a lithiasis risk indicator. For the calculation of the BRI a 40 millimolar ammonium oxalate solution is added to a urine sample, in a standardized procedure, until calcium oxalate crystallization occurs. The millimolar oxalate (Ox ~ 2) concentration, added to the urine sample up to that point, is determined and refers to a sample volume of 200 ml. The concentration of oxalate (Ox ~ 2) with respect to a sample volume of 200 ml is designated among medical specialists as an added quantity of oxalate (Gx ~ 2). Additionally, the initial concentration of free calcium ions in the urine sample [Ca2 +] is determined; the concentration is indicated in mmol / 1. The BRI is then calculated as BRI = [Ca2 +] / (Ox-2).

As a risk limit for the formation of calcium oxalate stones, a BRI of l / L is considered. All of the samples are classified as one of eight risk classes, I-VIII. BRI l / L separates risk classes IV and V. In a variation of the measurement procedure the risk of urinary calculus calcium phosphate formation can also be determined by supplying a phosphate solution to the urine sample, instead of a solution of ammonium oxalate, until its crystallization, and the ratio between free calcium ions and the phosphate solution is determined as an indicator of risk. The object of the invention is to specify a device and a method for the analysis of liquid samples, with which, in particular, the method of analysis previously described for a urine sample, for the determination of the Bonn Risk Index, can be carried out rationally and surely in a medical consultation or in a clinic. The device should make possible a standardized and widely automated execution of the procedure, with at the same time, reduced costs. The inventors have identified that for the determination of the crystallization point of a liquid sample a volumetric analysis system can be used in conjunction with an optical transmission measurement. But the measurement arrangement, for a transmission measurement, must not again demand the need to use exclusively sample containers for the liquid sample, in particular, for a high-quality, urine sample of urine. From this the inventors have deduced that a part of the liquid sample must be analyzed with a beam of light for the transmission measurements, but that on the other hand it is not advantageous to irradiate the sample container itself. Therefore, according to the invention, the device comprises a measuring head, which comprises a light conductor, and which can be immersed in a sample to be measured. A first end of the light conductor is assigned to a light source. A light sensor is arranged defined by the path of light, marked by the light conductor, of the light sent by the light source. In addition, a slit is provided in the submerged area of the measuring head, which houses the light conductor so that at least a part of the light conducted by the light conductor passes through the liquid sample along a defined path. A clouding of the liquid to be analyzed, to which the beginning of the crystallization must be attributed by the definite addition of an evaluation liquid in the liquid sample by means of a volumetric analysis system of the measuring device, can then be detected by the light sensor, cause of increased transmission losses. A beam-shaped light source is preferably used as a light source, this can be achieved, for example, by means of a diaphragm structure for an extended light source, or by the use of a laser, for example, of a laser diode . Furthermore, in the present application, the concept of a light source is not limited only to the spectrum of visible wavelengths, but a source for electromagnetic radiation outside the spectrum perceived by the human eye can also be used., for example, a source of infrared light. Preferably it will be visible light, in particular in the red region of the spectrum, preferably around 650 nm. A detector system according to the light source is used as the light sensor, which may be, for example, a phototransistor, a photodiode or a photoresist. It is also conceivable to carry out the photosensor as a sensor matrix, in this way the influence of error can be reduced by adjusting the sensor arrangement. The measuring head is now configured in accordance with the invention, so that it is assigned to the ends of the light conductor of the light source and to the light sensor, however, it can be separated from them. Especially preferable will be the use of a measuring head, which is used in the sense of a single-use measuring head, each time for a urine sample. The advantage in particular of such a method is that the measuring head which comes into contact with the liquid sample must not be cleaned up after a measurement. In addition, it must not be made as a single-use piece to be appropriate for multiple steps of measurement and cleaning. In relation to its geometrical configuration, the measuring head is made, so that it is immersed in a urine sample, at least until a slit in the measuring head, which is crossed by the light beam, is filled by the liquid to be measured, in particular, urine. Furthermore, it is preferred to arrange the light source and the light sensor, so that they do not come into contact with the liquid sample, that is, only the measuring head, which touches the liquid sample, is subject to fouling, but the which is in this inadvertible sense, because it is anyway an exchangeable part after a measurement. A possible configuration of the measuring head comprises a light conductor with at least one device for beam deflection. From here results the possibility of positioning both the light source and also the light sensor above the liquid level of the urine to be analyzed. As particularly advantageous, two beam deflectors have been shown, which are at an angle of 45 ° to the horizontal, and at an angle of 90 ° to one another, so that essentially one segment of the measuring head is formed. beam passage vertically downward, followed by an essentially horizontal beam and a beam passage segment directed essentially vertically upwards. In at least one of these beam passage segments is the aforementioned slit in the measuring head, so that the light beam penetrates essentially free in a certain segment through the liquid sample to detect changes on this known path in relationship to the transmission.

With the aid of a similar device according to the invention it is now possible to determine, in conjunction with a dosing system for the crystal formant, that amount of crystal formant leading to the start of crystallization. A solution containing a lithogenic component of the crystalline type, whose crystallization risk is to be determined, is used as the preferable crystal formant for a sample. For a urine sample, an oxalate or phosphate solution is preferred as the crystal formant. For the measurement of the necessary amount of crystal formant, in proportion to the volume of the liquid sample, it is necessary to establish the amount of liquid present in the urine to be analyzed. This can be determined by a weighing device with known weight of the sample container. Alternatively, the geodesic height of the liquid level in the sample container can be measured for determining the volume of the liquid to be measured with a known shape of the measuring container. For this, different devices can be thought of, for example, humidity sensors, which have a pair of electrodes between which a contact is made through the liquid to be measured, which can again be detected by means of a resistance measurement. Especially preferred will be a device for determining the geodetic height of the liquid level, which is connected to the measuring head for the transmission measurement. Then, the measuring head is preferably connected again with a height adjustment device, by which it is possible to drive the measuring head from above to the sample container, and with that, immerse it in the urine. If the height-adjustable device is made so that it is measured by a known reference height of the path traveled in the vertical direction, then the geodetic height of the liquid level can be determined at a known position of the liquid sensor and thereby the volume of liquid in the sample hosting area. In a particularly preferred embodiment of the invention, the slit in the measuring head is used for determining the position of the liquid level of the urine sample. The head at the beginning free, that is, in the slot provided for the measurement of the transmission, no liquid is found, it moves vertically downwards in the direction of the liquid level until the liquid penetrates to analyze in the slit and changes the transmission . By the known position of the slit and of the beam of light circulating there, as well as, the distance traveled can be determined later the situation of the liquid level. The value needed for the calculation of BRI for free calcium ions [Ca2 +] is determined in another preferred embodiment of the device for the analysis of a urine sample with the aid of a system of appropriate sensors. For this purpose, in a possible embodiment, a certain amount of the untreated urine sample is taken from the sample container, and by means of a fluidic system it is supplied to a Ca2 + ion sensor. This can be, for example, an ion-selective field effect transistor, which comprises an ion-selective membrane. Preferably, the fluid system also comprises a device for conducting the washing liquid for cleaning purposes. Additionally, to calibrate the sensors, it is preferred to provide them with a calibration solution. The pumps, tanks and collector vessels required for this, as well as the corresponding fluidic control, must be carried out according to the specialized knowledge. For control of the device according to the invention, this can comprise internal or external control units, in the form of microcontrollers or externally connected PCs, by which an interface for the user can also be realized in the form of a data input unit and displays. Preferably, the measuring head has a clamping device for supporting it in a clamping housing of the device, the clamping device having a clamping means, in particular, a positive joining component with a controlled breaking point, which is made So only a single use of the clamping equipment is given. This requires the use of a single use of the measuring head. Repeated misuse of a measuring head, which can lead to non-cleaning due to falsified results, is thereby avoided. Then, a repeated use of the measuring head is discarded in a particularly safe manner if the clamping means becomes unusable after the first use of the clamping device for supporting. In a variant embodiment, the measuring head is designed in such a way that it conducts the light received from the light source to the light sensor. In this way, a modification of the transmission of the liquid sample to be analyzed can be determined. Alternatively, the measuring head can be designed so that it conducts the light received from the light source along an optical path, with respect to the one adjacent to the sensor, but in which the sensor is not directly arranged. A measurement head embodiment of this form can be used to measure diffuse light that is produced by the liquid sample. The device can have a drive device for moving the relative measuring head relative to the sample container, with at least a portion of a determination device for determining the liquid level of the liquid sample being provided in the measuring head. . In order to simplify the exchange of the sample container, it is still advantageous if the measuring head can move relative to the sample container. This movement can be used elegantly in the variant mentioned above, at the same time, for the determination of the liquid level. If the slit in the measuring head represents a part of the determination equipment, the light source and the light sensor can be brought together with this slit for the determination of the liquid level, because the luminous intensity of the light sent by the light is modified. the light source and conducted through the measuring head when entering the slit in the sample to be analyzed. A fluid channel of the fluid system can be made in the measuring head. Then, a portion of the liquid sample can be sucked through the measurement head for the determination of a parameter of the liquid sample to be analyzed through the fluid channel. In a change of the measuring head, this suction fluid channel is also changed, which facilitates a pure clamping of the measuring device. The liquid channel is preferably closed by means of a stuffing box, which is passed through the measurement position of the measuring head via a flow section of the fluid system on the housing side of the measuring head. With the aid of a stuffing box of this type, a clean seal of the fluid channel is possible in front of the driving section. In a preferred variant, a fluid channel of the volumetric analysis system is made in the measuring head. Then, a separate volumetric analysis feeding tube can be omitted in the sample container. Preferably, a stirring device is provided for stirring the liquid sample, the measuring head having at least one flow component, in particular at least one flow blade, for interaction with the liquid sample. In this way, a defined mixture of the liquid sample is given by the agitation, and with it, a reproducible analysis of the liquid sample. In a variant of the measuring device, the measuring system for determining the concentration has a spectrometer. This makes it possible to determine the reliable and selective concentration in the product. With regard to the procedure, the task of the invention is thus solved on the one hand, by a method for the analysis of a liquid sample by volumetric analysis, which uses the measuring device according to the invention, described above. In addition, this task is solved by a procedure for the analysis of a liquid sample by volumetric analysis with the following steps: preparation of the liquid sample, measurement of the liquid level of the liquid sample by the introduction of a measuring head from above in the liquid sample, determination of the concentration of at least one type of ions of the liquid sample, measurement of a crystal formant in the liquid sample and measurement of the transparency of the liquid sample in accordance with the dosage. In this way a defined and reproducible liquid parameter determination is given. Preferably, a new single-use measuring head is used before dosing. This guarantees particularly well, as far as the measuring head is concerned, reproducible process conditions. A cleaning of an already used measuring head is eliminated. Preferably, a concentration determination sensor is calibrated prior to concentration determination. This provides definite relationships in the concentration determination, so that concentration determination sensors that tend to drift in the long term can also be used. Before the determination of the concentration, the liquid sample can be stirred. This guarantees defined measurement conditions, because a liquid sample is homogeneously distributed.

Preferably, a sample parameter of the measured values of concentration and transparency is calculated. This allows the indication of a crystallization point independent of the concentration by a simple numerical value. Preferably, the pH value of the liquid sample is further determined. This provides additional information about the composition of the liquid sample. In addition, the temperature of the liquid sample can be determined. This can be used in particular for the correction of the determined concentration. Additional liquid parameters can still be measured with the aid of the measuring device. The measuring device can be realized in an advantageous variant as a mobile laboratory for the determination of multiple parameters of the liquid. Parameters of the liquid of this type can be: The specific weight, the content in or the presence of Na, K, g, NH4, Cl, P04, S04, creatine, uric acid, leukocytes, nitrites, albumin, proteins, glucose, ketone , urobilin, bilirubin, urobilirubin, erythrocytes, hemoglobin, In addition, the precipitation of seroproteins, such as for example albumin, transferrin, globulin, immunoglobulin and fragments of immunoglobulin can be recorded. The invention is described in detail by the following figures, which show exemplary embodiments. Figure 1 shows the optical measurement system for the determination of the crystallization point. Figure 2 shows a sample receiving area with a sample container and a sample receiving plate, as well as the optical measurement system, according to Figure 1 and the corresponding positioning equipment. Figure 3 shows the volumetric analysis dosing system. Figure 4 shows the fluidic system. Figure 5 is a schematic external view of the measuring apparatus. Figure 6 shows a view similar to figure 1 of an alternative measuring head for an optical measurement system. Figure 7 shows a view in accordance with the visual line VII in figure 6. Figure 8 shows a cut according to the line VIII-VIII in figure 7. Figure 9 shows a view in accordance with the visual line IX in the figure 6. Figure 10 shows a view of the measuring head from above according to Figure 6.

Figure 11 shows a cut in accordance with the line XI-XI in figure 9. Figure 12 shows a procedure development schematically for the analysis of a liquid sample by volumetric analysis.

Figure 1 shows schematically an optical measurement system for the volumetric analysis, for the determination of the crystallization point. A measuring head 1 receives light from a light source 2 and conducts it to a light sensor 3. The measuring head 1 is embodied as an interchangeable unit, in particular as a single-use unit. In addition, the measuring head allows an arrangement of the light source and the light sensor 3 above the level of the liquid sample. The beam deflector required for this of the measuring head can be achieved, for example, according to FIG. 1, by two reflection surfaces 6.1 and 6.2, arranged at an angle of 45 ° with respect to the vertical and an angle of 180 ° one with respect to the other. Other embodiments are conceivable, for example, the use of an essentially horizontal reflecting element in the foot area of the measuring head and a V-shaped beam configuration. It is preferable for the lighting light to leave the light source with one component. direction directed vertically downwards, and light is returned to the light sensor with a steering component directed vertically upwards. In this manner and manner, the measuring head 1 can be immersed in the liquid sample without the light source 2 and the sensor 3 getting dirty. Preferably, the coupling of an essentially beam-shaped light beam will be in the measuring head. This is therefore composed of a transparent material for the used wavelength of the illumination light, for example P MA (methyl polymeth- acrylate) or makrolon (polycarbonate), which have a transparency for visible light of 70-81%. In general, all plastics manufactured in an injection molding process or with processes with chip removal can be used. Alternatively, the light conductor can also be made of glass. In most cases, the influence of diffused light can be left aside for the measuring head, and then only those outer areas, in which a beam deflector acts, should be advantageously metallized by aluminum vaporization. Alternative embodiments of the measuring head contain glass fibers or optical fibers of polymer bases for beam conduction. Furthermore, it is conceivable to separate the opposite driving regions of the beam from one another by means of the geometric realization of the measuring head. This can occur, for example, by means of a slit, which separates a first area of the measuring head with a beam line directed downwards from a second part, in which the beam line is directed upwards. Owing to the realization of a separation surface of the material of the measuring head with respect to the open area in the groove, crosstalk is avoided which decreases the measurement accuracy between the individual areas of the beam conduction in the measuring head. A similar free area 31 is shown in FIG. 1. For the execution of the transmission measurements, it is necessary to interrupt the light conductor through a determined path of the radiation. According to FIG. 1, a slit 5 in which the liquid to be analyzed penetrates in the submerged state should preferably be provided in the measuring head 1. This slit 5 and the liquid that is there are then traversed transversely by the beam of light. This is then coupled back to the measuring head or the light conductor of the measuring head and is supplied to the light sensor 3. Figure 2 shows in a longitudinal section the sample receiving area 7 for housing a sample container 8, which is positioned on a sample plate 9. Sampling plate 9 is positioned, so that it provides a possible horizontal base for the sample container 8, to determine if possible exactly the position of the level of liquid. In addition, a motor 10 is assigned to the sample dish 9 to enable a rotational movement for the mixing of the liquid sample in the sample container 8. In a preferred embodiment, the sample dish 9 is operated indirectly, this can be achieved, for example, by means of a magnetic drive. With this measure it is possible to seal the sample receiving area 7 for hygienic reasons against the outside area. In particular, the zone 7 can be projected laterally to the housing, so that the exit of liquids to the interior area of the appliance is absolutely ruled out. Above the sample container 8, in the sample receiving area 7, the measuring head 1 for the transmission measurement is located. This is fixed to a support of the measuring head 11 and can preferably be exchanged in the direction of a single-use article with simple handles. The light source 2, which remains permanently in the measuring system, and the light sensor 3 are preferably mounted in the measuring head 11. Furthermore, in a preferred embodiment, a marking and / or marking system is assigned to the measuring head. detection, with the help of which a measuring head 1 is identified as already used, or a measuring head is marked as used when embedding or immersing it in the liquid sample. In a possible embodiment, two breakable plastic terminals are mounted in the measuring head, which actuate a switch when inserted in the support of the measuring head. Thus, the terminals are broken, so that the switch is not tripped in a new use. The switch gives two signals to the electronics. The first signal is short-lived, the second signal is applied during the total measurement process and at the same time serves to control the position of the measuring head. For the positioning of the measuring head 1, the support of the measuring head 11 is connected to a positioning system 12 which essentially allows a vertical movement to immerse the measuring head 1 in the liquid sample. For carrying out the analysis it is necessary to determine the liquid volume of the liquid sample in the measuring vessel 8. This can be achieved in a different way and manner. On the one hand it is possible to derive the volume from a weight determination of the filled sample container 8. For this purpose, a weighing unit can be assigned to the sample plate 9. Alternatively, the volume can be measured in a known manner from the sample container by determining the geodesic height of the liquid level of the liquid sample in the sample container 8. Especially preferably it will be an embodiment in which a liquid detection system 14 is connected to the measuring head, and a position measuring system 13 is assigned to the measuring head 12 for the measuring head 13. Then, starting from a given reference point, the distance traveled by the measuring head can be approximated. 1 in the vertical direction, until reaching the liquid level for the determination of the volume of the liquid sample in the sample container 8. In a possible embodiment, the position measurement system 13 comprises installation switches for the reference position . These can be performed, for example, as reverberation sensors. In addition, the distance traveled from the measuring head for positioning can be determined by an appropriate sensor, for example, a rotation ratio sensor or a linear measurement system. If a stepper motor is selected as drive, the need to use additional sensors for the determination of the movement is eliminated. Figure 3 shows in a schematically simplified way the dosing system, assigned to the volumetric analysis system, for the dosing of a crystal formant in the liquid sample. To produce a crystallization of calcium oxalate, a solution of 0.04 N ammonium oxalate is preferably added as a crystal formant. If, instead of this, a crystallization of calcium phosphate in human urine should be analyzed, the ammonium oxalate solution is replaced by a phosphate solution. In a possible embodiment of the dosing system, the controlled and exact volume addition of the crystal formant is carried out by the admission of a reservoir of service medium, in which the crystal formant is located, with a fixed overpressure. This is produced by a pump 19, and is monitored by a pressure sensor 20. By a withdrawal line immersed in the liquid, which is under pressure, in the service medium reservoir 17, the crystal formant is directed through from a filter 18 to a nozzle 16, by which the controlled addition of the crystal formant is then carried out in the sample container 8 and the liquid sample therein. Alternatively, the dosing of the glass formant can be carried out, instead of applying the pressure of the service medium reservoir 17, by means of a dosing pump not shown in FIG. 3. Other methods of precise addition of volume can also be chosen. for the execution of the measurement procedure. It is preferred to stir the liquid sample during the dosing process. This can be caused by rotating the sample container, then working the measuring head 1 immersed in the liquid sample in the direction of a flow breaker. Figure 4 shows the fluidic system in a schematically simplified form and manner of the measuring device. It is useful to analyze other parameters of the liquid sample, in the case of urine the content of free calcium ions is particularly interesting. Additionally, the urine temperature and the pH value can also be determined. To do this, a certain fraction of the liquid sample is taken from the sample container, this can happen automatically or happen by the user, and is conducted to the fluidic system, the conductions of this fluidic system presenting a depression, so that a switching of the liquid transport can be caused by a switching of the valves 23.1, 23.2 and 23.3. to the intermediate tank 21. In this the necessary depression is produced by a pump 22 for air. By this measure both the liquid sample and other liquids can be conducted, for example, a first calibration solution 27 and a second calibration solution 26, as well as a cleaning solution 25 through the sensor block 24. Ventilation is also possible. of the channels for cleaning purposes through the air supply 28. Alternatively to the use of a depression in the fluidic system, a pump, for example a hose pump, can be used to transport liquid. This embodiment is not further represented in Figure 4. In the sensor block 24, ion-selective field effect transistors (ISFET) are preferably used, whose ion selectivity is produced by the choice of an appropriate membrane. Additionally, sensors used in a beneficial way are a pH sensor and a temperature sensor. In figure 4 the details of the signal and control conduction are not represented. A control of the device can be effected, for example, by one or more microcontrollers, which can also process the signals of the sensors. The measuring system can be realized as an autarkic unit, but it is also conceivable to transfer determined tasks and control tasks, for example, for the formation of an interface with the user or for printing functions, to an external control device or a PC In figure 5 a total view of the measuring device is shown. A housing is shown, in which the transmission measurement system with the interchangeable measuring heads and the dosing system for the execution of the volumetric analysis measurements are placed. Additionally, the device comprises a fluidic system for taking samples with other sensor elements, in particular for measuring the content of free calcium ions, as well as the pH value and the temperature of the liquid sample. For a user, only the sample receiving area for the introduction of a sample container is accessible. This sample receiving area is preferably made of stainless steel, so that simple cleaning is possible. In addition, an embodiment is preferred, for which at least partial areas of the sample receiving area 7 are covered with a layer of titanium oxide. This has, in particular, in conjunction with ultraviolet radiation antibacterial effects, so that automatic disinfection of the sample housing area can be performed. For this purpose, an ultraviolet light source is integrated in the zone of the sample receiving area 7, so it is preferred to close the sample receiving area with a door element that is hermetic to ultraviolet radiation for user protection. In addition to the use of the device according to the invention for the analysis of human urine, in particular, for the determination of BRI, an analysis of multiple different liquids is possible in which a change of the substances is produced by the addition of a substance. transmission properties, and for which a quantitative determination of this transmission modification must be made. Figure 12 shows a development diagram for carrying out the procedure for the analysis of a liquid sample, such as, for example, a human urine sample, by means of volumetric analysis.

In a preparation step 32, the measuring device is plugged in. Then, in a step of entering data 33, the introduction of data of the starting parameters, for example, of a patient identification code, through an alphanumeric keyboard takes place. The parameters entered can be controlled by the user through an LCD indicator of the measuring device. After data entry, the measuring head 1 is placed in a corresponding measuring head housing of the measuring device in a mounting step 34. The measuring head 1 has a contact tip not shown, which interacts with a corresponding contact in the mounting housing of the measuring device. While the measuring head is not correctly positioned in the housing, the measuring device automatically emits an error message on the LCD display. Then, in a preparation step 35, the sample container 8 with the liquid sample is placed on the sample tray 9 and then the door element 30 is closed. Also the closing position of the door element 30 is shown by a corresponding contact of the measuring device. If the door element 30 is not closed correctly, the measuring program issues an error message. Then the measurement starts automatically. Then, in a level measurement step 36, the liquid level of the liquid sample is measured. For this, the measuring head is brought from a defined zero position with the aid of the positioning system 12, which comprises a threaded spindle, above the sample container with the liquid sample. With the help of the positioning system 13, the elevation traveled by the number of turns of the threaded spindle is exactly measured. As soon as the slit 5 is wetted by the liquid sample, that is to say, as soon as the lower edge of the slit 5 is at the level of the liquid level, the intensity of the ray incident on the light sensor 3 is modified, because, on the one hand, the refractive coefficient on the separation surface of the slit 5 is modified, and because, on the other hand, the light beam is at least partially weakened through the liquid. The intensity change caused after reaching the liquid level is recorded by the light sensor 3. As soon as a defined modification begins, as soon as, for example, the measured intensity reaches less than 98% of the starting intensity, registers the current position of the threaded spindle by the positioning system 13. In this way, the liquid level of the liquid sample in the sample container 8, and of the height of the liquid level and the volume of liquid subsequently known, can be precisely determined deduct the sample amount in the sample container 8. Now the cleaning step 37 is carried out for the preparation of the concentration determination. To do this, the cleaning solution is passed briefly through the sensor block 24. Then, the cleaning solution 25 remains briefly in the fluidic system, so that the bacteria can be eliminated. This passage and permanence of the cleaning solution 25 is repeated several times during the cleaning step 37. With prolonged non-use of the measuring device it may also be necessary to clean other duct areas of the fluid system and not only the sensor block 24. In a subsequent calibration step 38, the sensor block 24 is calibrated. To this end, an ion sensor Ca and the pH sensor of the sensor block 24 are brought into contact with the first calibration solution 27. The first calibration solution 27 is passed through. Briefly by the sensors of the sensor block 24. As soon as the sensor values are stable, what the measurement program recognizes by a small variation of the consecutive measurement values, the measurement values are archived. This process is then repeated within the calibration step 38 with the second calibration solution 26. From the sensor measurement values thus determined for both calibration liquids 26, 27 different, the measurement program determines the calibration parameters necessary for the determination of the Ca concentration and for the determination of the pH value. The measurement values obtained below are corrected with the help of the calibration parameters obtained. Next, in the stirring step 39, the liquid sample is agitated in the sample container 8. For this, the sample dish 9 with the sample container 8 is placed in constant rotation around the vertical axis of the sample container 8. During the stirring step 39, the measuring head 1 is further lowered in the liquid sample and consequently acts as a stirrer. In a determination step of the following concentration, a portion of the liquid sample from the sample container 8 is sucked by an inlet line 41 (cf. FIG. 4) of the sample container 8 into the sensor block 24. The volume of samples aspirated briefly passing through the sensor block 24. After waiting for a set time of the Ca sensor of the sensor block 24, the Ca2 + concentration is measured with the Ca sensor of the sensor block 24. The pH value is measured with the sensor of pH of the sensor block 24. The temperature is measured with the temperature sensor. The temperature value is used to correct the concentration value of Ca using the measuring program. Now another cleaning step 42 is carried out for the sensor block 24. The cleaning step 42 corresponds to the cleaning step 37. In a measurement step of the crystallization 43, the sample container 8 is constantly rotated first with the aid of the motor 10 of the sample plate 9, so that a well-mixed liquid sample is present. Next, the light source 2 is started and the luminous intensity of the light source 2 reaching the light sensor 3 is measured. At certain time intervals, for example, at intervals of every minute or also at intervals for a few seconds, a certain amount of ammonium oxalate is injected or titrated, via the dosing system 15 of the service medium reservoir 17. From the known concentration of the ammonium oxalate solution, the measurement program calculates the total injected amount of ammonium oxalate. The volumetric analysis is continued in the measurement step - of crystallization 43, until a crystallization of calcium oxalate begins. The crystallization point can be recognized by a clouding of the liquid sample and a lower intensity linked to it in the light sensor 3. As a point of crystallization, for example, the point of volumetric analysis can be established in which the luminous intensity measured in the light sensor 3 has 98% of the luminous intensity at the beginning of the volumetric analysis. In the measurement step of the crystallization 43, the amount needed to reach the crystallization point of the ammonium oxalate added can be measured in this way by reducing the light intensity measured in the light sensor 3, with an accuracy of example, +/- 0.2 ml for a volumetric analysis speed of 40 mmol / 1. The calculation of the BRI index is then carried out in a calculation step 44. For this, the quantity of oxalate is first calculated from the amount of liquid in the liquid sample and the quantity of ammonium oxalate added to the point of crystallization. The BRI index results from, as mentioned at the beginning of the description, as a quotient of the Ca2 + concentration determined in the step of determining the concentration 40, divided by the amount of oxalate. As the quantity of oxalate is understood in medical circles the concentration of oxalate (Ox2 ~) with respect to a sample volume of 200 ml. Then, in a following file step 45, the following values are archived in particular: a patient identification code, the date, the time, the measured temperature, the measured Ca2 + concentration, the measured pH value, the calculated BRI index of the measurement data, the respective individual measurement value of the sensors of the sensor block 24, possibly error messages that have occurred. As a means of filing, a compact flash card is used in particular. For maintenance or monitoring purposes, the archive medium can be transferred to a maintenance or monitoring computer through a reading interface.

In a last printing step 46, the desired data of the measured, calculated or filed values are printed. For this, the archived information can be transferred to a computer, for example, via a USB interface. The data can continue working there. An alternative measuring head to the measuring head 1 shown in FIG. 1 is shown in FIGS. 6 to 11. Components of this measuring head, corresponding thereto, which were described above already with reference to FIGS. 1 to 5, or with reference to the description of the method according to figure 12, they bear the same reference numbers and are not explained individually again. The alternative measuring head has an anchoring groove 49, open in FIG. 6 to the left, which runs horizontally, in the fastening section 47 above in FIG. 6 in a side wall 48. The anchoring groove 49 component of a holding device for supporting the alternative measuring head 1 in a clamping housing of the measuring device. The holding housing also has a fastening rib complementary to the anchoring groove 49, which is not shown in the drawing. Another component of the clamping equipment is an anchoring terminal 50 disposed in the anchoring groove 49, which extends in Figure 6 horizontally and perpendicular to the extension direction of the anchoring groove 49. In the clamping housing of the device , the anchor terminal 50 interacts with a corresponding clamping opening of the measuring device therefor.

In the alternative measuring head 1, a fluid channel 51 is formed, which is in fluid connection with the intake line 41 of the fluid system in the mounted alternative measuring head 1. The fluid channel 51 extends in a first channel section 52 from a horizontal upper boundary wall in FIG. 6, from the slit 5 upwards to the holding section 47. There, the fluid channel 51 has a deviation of 90. °, tapering first in the junction in that deviation and then extending in the form of a cone in a second section of channel 53. Through a subsequent widening by steps the second channel section opens onto a side wall 55 on the left in figure 6 of the alternative measuring head 1. Before the alternative measuring head 1 is inserted, the fluid channel 51 is closed by means of a stuffing box, not shown, which is placed in a sealed manner in the widening 54. In the measuring position of the alternative measuring head 1, in the that it is housed in the clamping housing of the measuring device, the cable gland is traversed by a section of conduction of the intake line 41 of the fluidic system on the housing side of the measuring head. This section of conduction is formed by a usual injection needle in the market. In accordance with the perforation of the stuffing box with the conduit section, the stuffing box seals the conduit section in front of the inner wall of the broadening 54, so that there is a sealed fluid connection out of the fluid channel 51 with respect to the conduit of the conduit. admission 41. In a lower deviation section 56 in FIG. 6, both beam deviators 6.1, 6.2 are directly adjacent to each other, so that the deviation zone 56 is in the form of a roof edge standing on the head. . In both beam deflectors 6.1, 6.2 is formed on a respective side projecting a flow fin 57. Both flow fins 57 serve as a flow component that interacts with it during the agitation of the liquid sample for the mixture. By inserting the alternative measuring head 1 into the measuring position, the anchoring terminal 50 fits into the corresponding opening of the clamping housing of the measuring device. The opening is formed here so that in the withdrawal that is carried out once the measuring head measurement is made, the anchoring terminal 50 breaks at a controlled breaking point separating from the holding segment 47. As the anchoring terminal 50 has a clamping function, another use of the alternative measuring head is not possible after the break. In the alternative measuring head 1, the slit 5 serves, as described above in relation to the development scheme according to FIG. 12, for the determination of the liquid level of the liquid sample. For this reason, the slit 5 together with the positioning system 12 forms the positioning system 13, the light source 2, the light sensor 3, as well as the beam deflectors 6.1, 6.2, a determination equipment for determining the liquid level of the liquid sample. Both variants of the measuring head, which are represented, on the one hand, in FIG. 1 and, on the other hand, in FIGS. 6 to 11, are respectively designed so that they conduct the light received from the light source 2 directly to the light sensor 3. In another variant of the measuring head, not shown, it is configured in such a way that it conducts the light received from the light source 2 along an optical path, with respect to which the sensor is arranged adjacent to it. of light 3, but the sensor is not directly arranged in the optical path. In this case, the light sensor 3 does not measure any modification of the transmission that occurs by the beginning of the crystallization of the liquid sample, but changes in the diffuse light intensity caused in this way. The light sensor 3 can be arranged, for example, so that it first measures no light intensity of the light source 2 in a non-dispersing liquid sample. Only due to the scattering caused by the crystallization that begins, diffuse light arrives until the light sensor 3, which can then be designed in a correspondingly sensitive manner, so that it can register small amounts of diffuse light.

In another variant of the measuring head (not shown), a fluid channel of the dosing system or volumetric analysis 15 is made with the nozzle in the measuring head. In another variant of the measuring head, a spectrometer is used in place of the sensor block 24 for the determination of the Ca2 + concentration in the step of determining the concentration. For this purpose, the part of the liquid sample, whose concentration of Ca2 + must be determined, is irradiated with light of different wavelengths, deduced by the absorption of the liquid at determined wavelengths the presence of Ca ions in a corresponding concentration. List of reference drawings 1 Measuring head 2 Light source 3 Light sensor 4 Light path 5 Slit 6.1, 6.2 Beam diverter 7 Sample receiving area 8 Sample container 9 Sample plate 10 Motor 11 Measurement head holder 12 Positioning system 13 Position measurement system 14 Liquid detection system System of two je 16 Nozzle 17 Deposit of service medium 18 Filter 19 Pump 20 Pressure sensor 21 Intermediate tank 22 Air pump 23 Valves 24 Sensor block 25 Cleaning solution 26 First calibration solution 27 Second calibration solution 28 Air supply 29 Housing 30 Door element 31 Open area in measuring head 32 Preparation step 33 Data entry step 34 Mounting step 35 Preparation step 36 Level measurement step 37 Cleaning step 38 Calibration step 39 Stirring step 40 Concentration determination step 41 Admission drive 42 Cleaning step 43 Measurement step of crystallization 44 Step calculation 45 File step 46 Printing step 47 Clamping section 48 Side wall 49 Anchoring slot 50 Anchoring terminal 51 Fluid channel 52 First channel section 53 Second channel section 54 Expansion 55 Side wall 56 Deviation section 57 It is noted that in relation to this date the method known by the applicant to carry out the aforementioned invention, is the clear one of the present description of the invention.

Claims

Claims Having described the invention as above, the content of the following claims is declared as property: 1. Device for the analysis of a liquid sample by volumetric analysis, characterized in that it comprises 1.1 a light source; 1.2 a light sensor; 1.3 a submersible measuring head in the liquid sample to be analyzed, with a light conductor, which receives and conducts light from the light source, the measuring head having a slit with an interruption of the light conductor, into which the liquid to be analyzed with the submerged measuring head; 1.4 it being possible to separate the measuring head from the light source and from the light sensor; and 1.5 a volumetric analysis system for the defined addition of a liquid titration in the liquid sample. Device for the analysis of a liquid sample according to claim 1, characterized in that a device for the dosing of a crystal formant, comprising a lithogenic component of a certain type of crystal, is provided in the liquid sample. Device for the analysis of a liquid sample according to one of claims 1 or 2, characterized in that the liquid sample is urine. 4. Device for the analysis of a liquid sample according to claim 3, characterized in that the crystal formant contains oxalate or phosphate. Device for analyzing a liquid sample according to at least one of claims 1 to 4, characterized in that the device comprises a measuring system for determining the concentration of at least one type of ions in the liquid sample. Device for analyzing a liquid sample according to claim 5, characterized in that the measuring system determines the concentration of ions of a lithogenic substance in the measuring liquid. Device for the analysis of a liquid sample according to claim 6, characterized in that the concentration of Ca 2+ ions in the liquid sample is determined. Device for the analysis of a liquid sample according to at least one of claims 5-7, characterized in that at least one ion-selective d effect transistor is used for the determination of the ion concentration. Device for the analysis of a liquid sample according to at least one of claims 1 to 8, characterized in that the device comprises a measuring system for measuring the pH value of the liquid sample. 10. Device for the analysis of a liquid sample according to at least one of claims 1 to 9, characterized in that the device comprises a temperature measurement system for measuring the temperature of the liquid sample. Device for the analysis of a liquid sample according to at least one of claims 1 to 10, characterized in that the device comprises a fluidic system for the defined taking of a quantity of liquid to be analyzed. Device for the analysis of a liquid sample according to claim 11, characterized in that the fluidic system comprises a device for calibration with at least one calibration liquid. Device for the analysis of a liquid sample according to claim 10, characterized in that the fluidic system comprises means for cleaning. Device for the analysis of a liquid sample according to one of claims 1 to 13, characterized in that the interchangeable sample container is provided for receiving the liquid sample. Device for analyzing a liquid sample according to claim 14, characterized in that the device comprises a sample receiving area, in which the sample container can be arranged essentially below the measuring head. Device for the analysis of a liquid sample according to claim 15, characterized in that the sample receiving area is constructed of stainless steel and / or has a coating of titanium oxide. 17. Device for the analysis of a liquid sample according to claim 15 or 14, characterized in that the sample receiving area comprises a device that disinfects them by means of ultraviolet light. 18. Device for the analysis of a liquid sample according to at least one of claims 12 to 17, characterized in that a rotating sample plate is provided for the sample container with an indirect drive. 19. Device for the analysis of a liquid sample according to at least one of claims 1 to 18, characterized in that the measuring head is a single-use article. 20. Device for the analysis of a liquid sample according to claim 19, characterized in that an equipment is provided which marks a used measuring head for single use and / or distinguishes an already used measuring head. Device according to one of Claims 1 to 20, characterized in that the measuring head has a clamping device for supporting the clamping means of the device, the clamping device having a clamping means, Particularly, a component of positive connection, with a predetermined breaking point, which is realized so that only a single use of the clamping equipment is given 22. Device according to one of claims 1 to 21, characterized in that the 23. The device according to one of claims 1 to 21, characterized in that the measuring head is designed in such a way that it conducts the measuring head in a manner that conducts the light received from the light source to the light sensor. light received from the light source along an optical path, with respect to the one adjacent to the sensor, but in which the sensor is not directly arranged 24. Device according to claim 14, characterized by a drive device for moving the measuring head relatively to the sample container, with at least one part of a determination device for the measurement being provided in the measuring head. determination of the liquid level of the liquid sample. 25. Device according to claim 24, characterized in that the slit represents a part of the determination equipment. 26. Device according to claim 11, characterized in that a fluid channel of the fluid system is made in the measuring head. 27. Device according to claim 26, characterized in that the liquid channel is closed by means of a stuffing box, which is passed through in the measurement position of the measuring head by a fluid-system driving section of the head housing side. of measurement. Device according to one of Claims 1 to 27, characterized in that the fluid channel of the volumetric analysis system is made in the measuring head. Device according to one of claims 1 to 28, characterized by a stirring device for agitating the liquid sample, the measuring head having at least one flow component, in particular at least one flow blade, for the interaction with the liquid sample. 30. Device according to claim 5, characterized in that the measuring system for determining the concentration comprises a spectrometer. 31. Procedure for the analysis of a liquid sample by volumetric analysis, characterized in that a device according to one of claims 1 to 30 is used. 32. Procedure for the analysis of a liquid sample by volumetric analysis characterized in that it comprises the following steps: preparation of the liquid sample; measurement of the liquid level of the liquid sample by introducing a measuring head from above into the liquid sample; determining the concentration of at least one type of ions of the liquid sample; carrying out a measurement of the crystallization by measuring a crystal formant in the liquid sample and measuring the crystallization, preferably by measuring the transparency of the liquid sample after dosing. 33. Method according to claim 31 or 32, characterized by the use of a single-use measuring head before dosing. Method according to one of the claims | 31 to 33, characterized by the cleaning and / or calibration of a concentration determination sensor before the determination of the concentration. 35. Method according to one of claims 31 to 34, characterized by stirring the liquid sample before determining the concentration. 36. Method according to one of claims 31 to 35, characterized by the calculation of a sample parameter from the values measured with concentration and transparency. 37. Method according to one of claims 31 to 36, characterized by determining the pH value of the liquid sample. 38. Method according to one of claims 31 to 37, characterized by the determination of the temperature of the liquid sample.